Congestive heart failure is a fast growing health problem that mostly affects older adults. In this condition the heart is unable to pump enough blood to meet the needs of the body's organs. Among the most common causes of congestive heart failure can be mentioned coronary artery disease, causing myocardial ischemia, myocardial infarction and cardiomyopathy. During ischemia the cardiac relaxation, i.e. diastole, is changed or disturbed because the cardiac muscle is stiffened. A disturbed diastolic phase or diastolic failure is a very early sign of congestive heart failure, such that at this early stage it might not even appear as symptoms to the patient. If it would be possible to detect these early signs of disturbed relaxation patterns, the physician would be capable of taking actions preventing congestive heart failure to escalate which often will result in reduced systolic capacity.
In U.S. Pat. No. 4,905,696 it is described that the P-wave in the electrocardiogram can be detected as a rapid inflection or notch in a ventricular impedance signal. This phenomenon is used for providing P-synchronous heart stimulation of a patient's heart.
It is known that a notch appears in the impedance signal corresponding to early diastole of a cardiac cycle cf. Brian R. Pickett et al., The American Journal of Cardiology, vol. 71, May 1, 1993, “Usefulness of the Impedance Cardiogram to Reflect Left Ventricular Diastolic Function”. In this document a study is described of the correlation between a dip in a non-invasively measured impedance and Doppler measurements for diastolic studies.
FIG. 1 shows examples of measurements from animal tests, more precisely results from measurements on a sheep. Curve a shows an impedance signal measured with a standard bipolar pacing lead positioned in right ventricular apex as indicated in the figure. Curves b and c show the right ventricular pressure and the left ventricular pressure respectively. Curve d is the surface ECG and curve e shows the respiratory flow. As appears from the figure, a distinct notch is seen in the intracardiac impedance, marked by a circle in curve a, is seen in the majority of measurements. Its location is closely after the point where the ventricular pressure curves b and c are down to a minimum and prior to atrial systole, i.e. the notches are located in early heart diastole. In some measurements the notch occurs at the time of atrial systole which could lead to the conclusion that it is caused by atrial contraction. However, the notch is present even if no atrial activity is observed, i.e. even when no P-wave is available.
The impedance measured in human beings also exhibits a notch, marked by circles in FIG. 2, cf. also the above-mentioned document by Brian R. Pickett et. al. The diagrams a in FIG. 2 show the bipolar right ventricular impedance measured in humans with no prior history of coronary artery decease for three different tip-ring distances, viz 10, 20 and 30 mm respectively. Corresponding intracardiac ECGs are shown at b in the figure. The measurements shown in FIG. 2 are made during rest conditions with the patient lying down, and the curves shown are calculated from measurements during 10 or more heartbeats. As appears a distinct notch in the diastolic impedance is shown in all examples, and this notch is occurring after the end of the T-wave in the ECG, marking the start of relaxation or diastole, and before the appearance of the subsequent P-wave.
FIG. 3 shows another example of such bipolar right ventricular impedance measurements on a human being during rest conditions and drug-induced workload together with corresponding ECGs. Also in this case the curves shown are averaged curves of both the intracardiac electrogram and the impedance calculated from 10 or more heartbeats. A distinct notch in diastolic impedance is seen in all examples, marked by circles in the figure. Although the over-all impedance might show a slight change in morphology, little or no change in notch appearance between rest and load conditions is observed, the timing of the notch being earlier during load. Thus for a healthy patient the shape of the notch does not change significantly with the load, whereas the situation might be different for patients with cardiac abnormalities that alter the relaxation patterns.
FIG. 4 shows the right ventricular bipolar impedance i), the first time derivative of the impedance ii), and a corresponding loop plot iii) of these two signals. As appears there is very little variation in the impedance notch appearance. The three set of diagrams i, ii and iii, represent three different tip-ring distances, viz. 10 mm, 20 mm and 30 mm respectively.
To use such loops, formed by plotting parameter values against related time derivative values, as an aid for analysis of phenomena and functions of the heart is previously described in e.g. U.S. Pat. Nos. 5,427,112 and 5,556,419.
In FIG. 5 the unipolar impedance, i.e. the impedance measured between an electrode tip positioned in the ventricular apex and the casing of the implanted monitor is shown together with the corresponding time derivative of this impedance signal and the loop plot for a healthy patient in rest, curve a, for a load of 30 W, curve b, and a load of 75 W, curve c. Also in this case the occurrence of the notch in the impedance signal is evident.
FIG. 6 shows results from corresponding measurements on a patient with dilated cardiomyopathy. The curves a), b) and c) show the result from right ventricular unipolar impedance measurements in a patient during rest, curve a, a load of 30 W (cycling), curve b and a load of 60 W (cycling), curve c. The impedance signal Z, the first time derivative of the impedance dZ/dt and a loop plotted of these two signals dZ/dt and Z are shown. In these examples there is a marked change in the impedance notch appearance between rest and load situations, which is related to relaxation disturbances of the patient. The changes in the notch appearance are emphasized in the loop plots.
Animal tests comprising impedance measurements performed simultaneously with echocardiographic measurements of mitral blood flow also show the appearance of an impedance notch at the time for maximum inflow in early diastole, and prior to the ventricular filling caused by atrial contraction. It has also appeared that the time between ECG R-wave and the occurrence of an impedance notch correlate well with the heart rate in a physiological manner.
To sum up, tests show that the notch appearing in the diastolic impedance is related to a ventricular event, and not to an atrial event. In practically all tests the notches occur prior to atrial systole. In some cases the time interval between the T-wave in one heartbeat and the P-wave in the subsequent beat is short and in such cases the notch can be seen to occur simultaneously with the electrical P-wave, however, echocardiographic measurements of mitral blood flow show, as mentioned above, that the atrial contribution to ventricular filling occurs after the impedance notch, i.e. the notch is related to rapid ventricular filling in early diastole.